Posology : מינונים

4.2    Posology and method of administration

Posology
The physician should prescribe the most appropriate formulation and strength according to weight and dose. It is recommended to parent and care giver to administer Briviact oral solution with the measuring device (10 ml or 5 ml oral dosing syringe) provided in the carton box.

Adults
The recommended starting dose is either 50 mg/day or 100 mg/day based on physician's assessment of required seizure reduction versus potential side effects. The dose should be administered in two equally divided doses, once in the morning and once in the evening. Based on individual patient response and tolerability, the dose may be adjusted in the dose range of 50 mg/day to 200 mg/day.

Children (from 4 years of age) and adolescents weighing 50 kg or more The recommended starting dose is 50mg/day. Brivaracetam may also be initiated at 100 mg/day based on physician's assessment of need for seizure control. The dose should be administered in two equally divided doses, once in the morning and once in the evening.The recommended maintenance dose is 100 mg/day. Based on individual patient response, the dose may be adjusted in the effective dose range of 50 mg/day to 200 mg/day.

Children (from 4 years of age) and adolescents weighing less than 50 kg The recommended starting dose is 1mg/kg/day. Brivaracetam may also be initiated at 2 mg/kg/day based on physician's assessment of need for seizure control. The dose should be administered in two 
equally divided doses, once in the morning and once in the evening. The recommended maintenance dose is 2 mg/kg/day. Based on individual patient response, the dose may be adjusted in the effective dose range of 1 mg/kg/day to 4 mg/kg/day.

The following table summarises the recommended posology for children from 4 years of age and adolescents.

Children (≥4 years) and             Children (≥4 years) and adolescents ≥50 kg                  adolescents <50 kg

Administered in 2 equally             Administered in 2 equally divided doses                          divided doses
Therapeutic dose range         50 - 200 mg/day                       1 - 4 mg/kg/day Recommended starting dose      50 mg/day                             1 mg/kg/day (or 100 mg/day)*                      (or 2 mg/kg/day)*
Recommended maintenance        100 mg/day                            2 mg/kg/day dose
* Based on physician's assessment of need for seizure control.

The dose per intake for each patient should be calculated using the following formula: 
Volume per administration (ml) = [weight (kg) x daily dose (mg/kg/day) ] x 0.05 
The table below provides examples of volumes of oral solution per intake depending on prescribed dose and body weight. The precise volume of oral solution is to be calculated according to the exact body weight of the child.
Volumes of oral solution to be taken per administration
Weight
For a dose of       For a dose of           For a dose of        For a dose of 1 mg/kg/day         2 mg/kg/day            3 mg/kg/day           4 mg/kg/day 0.05 ml/kg/intake      0.1 ml/kg/intake       0.15 ml/kg/intake    0.2 ml/kg/intake (corresponding to     (corresponding to       (corresponding to   (corresponding to 0.5 mg/kg/intake)      1 mg/kg/intake)        1.5 mg/kg/intake)    2 mg/kg/intake) 10 kg           0.5 ml                 1 ml                 1.5 ml                 2 ml (5 mg)                 (10 mg)              (15 mg)                (20 mg) 15 kg           0.75 ml                1.5 ml               2.25 ml                3 ml (7.5 mg)               (15 mg)              (22.5 mg)              (30 mg)  20 kg           1 ml                   2 ml                 3 ml                   4 ml
(10 mg)                (20 mg)              (30 mg)                (40 mg)  25 kg           1.25 ml                2.5 ml               3.75 ml                5 ml
(12.5 mg)              (25 mg)              (37.5 mg)              (50 mg) 30 kg           1.5 ml                 3 ml                 4.5 ml                 6 ml (15 mg)                (30 mg)              (45 mg)                (60 mg) 35 kg           1.75 ml                3.5 ml               5.25 ml                7 ml (17.5 mg)              (35 mg)              (52.5 mg)              (70 mg)  40 kg           2 ml                   4 ml                 6 ml                   8 ml
(20 mg)                (40 mg)              (60 mg)                (80 mg)  45 kg           2.25 ml                4.5 ml               6.75 ml                9 ml
(22.5 mg)              (45mg)               (67.5 mg)              (90 mg) 50 kg           2.5 ml                 5 ml                 7.5 ml                 10 ml (25 mg)                (50 mg)              (75 mg)                (100 mg) 
Missed doses
If patients missed one dose or more, it is recommended that they take a single dose as soon as they remember and take the following dose at the usual morning or evening time. This may avoid the 
brivaracetam plasma concentration falling below the efficacy level and prevent breakthrough seizures from occurring.

Discontinuation
If brivaracetam has to be discontinued it is recommended to withdraw it gradually by 50 mg/day on a weekly basis. After 1 week of treatment at 50 mg/day, a final week of treatment at the dose of 20 mg/day is recommended.

Special populations

Elderly (65 years of age and above)
No dose adjustment is needed in elderly patients (see section 5.2).
The clinical experience in patients ≥ 65 years is limited.
Renal impairment
No dose adjustment is needed in patients with impaired renal function (see section 5.2). Brivaracetam is not recommended in end-stage renal disease patients undergoing dialysis due to lack of data.
Based on data in adults, no dose adjustment is necessary in paediatric patients with impaired renal function.

Hepatic impairment
Exposure to brivaracetam was increased in adult patients with chronic liver disease. In adults, a 50 mg/day starting dose should be considered. In children and adolescents weighing 50 kg or greater, a 50 mg/day starting dose is recommended. A maximum daily dose of 150 mg administered in 2 divided doses is recommended for all stages of hepatic impairment (see sections 4.4 and 5.2).
In children and adolescents weighing less than 50 kg, a 1 mg/kg/day starting dose is recommended.
The maximum dose should not exceed 3 mg/kg/day. No clinical data are available in paediatric patients with hepatic impairment.

Children less than 4 years
The safety and efficacy of brivaracetam in children aged less than 4 years have not yet been established.
Currently available data are described in section 4.8, 5.1, and 5.2 but no recommendation on a posology can be made.

Method of administration

Brivaracetam oral solution can be diluted in water or juice shortly before swallowing and may be taken with or without food (see section 5.2). A nasogastric tube or a gastrostomy tube may be used when administering brivaracetam oral solution.

Briviact oral solution is provided with a 5 ml and a 10 ml oral dosing syringe with their adaptor.

Oral dosing syringe (5 ml graduated every 0.1 ml) with an adaptor, recommended for use by patients weighing less than 20 kg or needing a maximum of 50 mg (5 ml) brivaracetam per administration.
The 5 ml oral syringe must be used in patients weighing less than 20 kg to ensure accurate dosing as the 10 ml oral syringe does not allow accurate measurements of volumes <1 ml.
One full 5 ml oral dosing syringe corresponds to 50 mg of brivaracetam. The minimum extractible volume is 0.25 ml which is 2.5 mg of brivaracetam. As from the 0.1 ml graduation mark, each graduation corresponds to 0.1 ml which is 1 mg of brivaracetam. Additional graduations at 0.25 ml and 0.75 ml starting at 0.25 ml up to 5 ml are shown.

Oral dosing syringe (10 ml graduated every 0.25 ml) with an adaptor, recommended for use by patients weighing more than 20 kg or needing a dose between 50 mg and 100 mg (5 ml to 10 ml) brivaracetam per administration.


One full 10 ml oral dosing syringe corresponds to 100 mg of brivaracetam. The minimum extractible volume is 1 ml which is 10 mg of brivaracetam. As from the 1 ml graduation mark, each graduation corresponds to 0.25 ml which is 2.5 mg of brivaracetam.

Instructions for use are provided in the package leaflet.